Urocortin inhibits mesenteric arterial remodeling in spontaneously hypertensive rats

Abstract

Urocortin (UCN), a newly isolated corticotrophin-releasing factor (CRF) related peptide, has been found to have potent cardiovascular protective effects. This study aimed to investigate the long-term effects of UCN on arterial remodeling and related functional alterations. UCN (7 μg/kg/d) was administered to spontaneously hypertensive rats (SHR) for 8 weeks. Systolic blood pressure (SBP) was measured weekly. Functional studies were performed on isolated mesenteric arterial segments. Also, by light microscope and electron microscope, the morphology of mesenteric arteries was examined. Our results showed that mean SBP in UCN-treated SHRs was about 40 mmHg lower than that of the control SHR group, and was similar to that of the enalapril-treated group. In the mesenteric arterial segments pre-contracted with norepinephrine (0.001-10 μM), the maximal relaxation rate induced by acetylcholine (10 μM) in UCN-treated group (about 93.3%) was higher than that in SHR control group (about 40.0%) (n = 6, P < 0.01). Furthermore examination under light microscope showed that UCN (3.5 μg/kg/d) treatment significantly reduced media thickness, media/lumen ratio, resulting in larger lumen diameter while analysis of transmission electron microscopic findings revealed that chromatin, internal elastic lamina and densely packed mitochondria displayed a close-to-normal distribution after UCN treatment. These results suggested that long-term UCN treatment not only had hypotensive effects but may also inhibited development of vascular remodeling in mesenteric arteries in SHR. © 2009 Elsevier Inc. All rights reserved.